This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to establish the structural foundations for manipulation and exploitation of self-organization encountered in biological matter to combine the natural characteristics of virus capsids with the exquisite physical properties of nanoparticles. The objective of this proposal is to conduct a systematic structural exploration of the influence of the nanoparticle surface chemistry on the assembly process and on the capsid structure of VLP's. VLP's have potential uses as autonomous, non-intrusive inter- and intracellular vectors and imaging probes with unprecedented spatial resolution, sensitivity, and specificity or as building blocks for hierarchical metamaterials which integrate the self-organizing principles of biological matter with the physical properties of inorganic nanoparticles. Another possible application is the development of improved vaccines, with the advantage of the absence of the viral genome. Progress towards the development and implementation of VLPs as a general research tool requires the study of the role of different parameters involved in the complex formation: nanoparticle template radius and surface chemical and physical properties. The role of these parameters can be understood by resolving the three-dimensional (3D) structure of VLP's by cryo-electron microscopy (cryo-EM). Recent theoretical work on virus assembly based on a reduced set of thermodynamic assumptions, has been successful in capturing the most salient features of empty capsids. Substantial progress has been made in the last decade in pushing the resolution of three-dimensional reconstructions from cryo-electron microscopy (cryo-EM) data, down to subnanometer resolution. Therefore, cryo-EM is an appropriate investigation tool to reveal the 3-D structure of VLP at resolutions that will allow an adequate understanding of their organization and properties.